FORMULATION AND EVALUATION OF OMEPRAZOLE FLOATING TABLETS

Dr chandra

CONTENTS Introduction Literature Review Aim and Objectives Material and Methods Results and Discussion Conclusion References

INTRODUCTION

Floating tablets: Floating systems (or) hydro-dynamically balanced systems

have a bulk density lower than gastric fluid and thus remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time. While the system is floating on the gastric contents, the drug is slowly released at a desired rate from the stomach. After the release of drug, the residual system is emptied from the stomach. This result in an increase in the gastric retention time and better control of fluctuations in the plasma drug concentration

ADVANTAGES The Gastroretentive systems are advantageous for drugs

absorbed through the stomach.  Irritation on the stomach wall caused by acidic

substances like aspirin can be avoided by using floating drug delivery system.

The Gastroretentive systems are advantageous for drugs meant for local action in the stomach

When there is a vigorous intestinal movement and a short transit time as might  occur in certain type of diarrhea, poor absorption is expected. Under such circumstances it may be advantageous to keep the drug in floating condition in stomach to get a relatively better response

DISADVANTAGES

Floating system is not feasible for those drugs that have solubility or stability problem in the G.I. tract.

These systems require a high level of fluid in the stomach for drug delivery to float and work efficiently.

The drugs that are significantly absorbed throughout the gastrointestinal tract, which undergo significant first pass metabolism, are only desirable candidate.

Some drugs present in the floating system causes irritation to the gastric mucosa.

LITERATURE REVIEW Raguia Ali Shoukri et. al studied on “Formulation and in vitro evaluation of combined floating mucoadesive tablet of

Omeprazole succinate”. Floating mucoadhesive tablet of Omeprazole succinate were developed to prolong its release and improve bioavailability and avoidance of first pass hepatic metabolism. Floating tablets were prepared by directly compressible polymer such as hydroxyl propyl methyl cellulose (HPMC) K4M, HPMC K15M, sodium carboxyl methyl cellulose and carbopol 940P and were evaluated for buoyancy test, mucoadhesion force, swelling study, drug content, Ex vivo mucoadhesion strength and in vivo release profile.

Gupta S.C et. al studied on “Development and in-vitro dissolution studies of bilayer tablet of Omeprazole succinate

(SR) and Hydrochlorothiazide (IR)”. In the immediate release formulation micro crystalline cellulose and starch were used as super disintegrant and was directly compressed. For sustained release portion HPMC polymers were used. The compressed bilayer tablets were evaluated for weight variation, thickness, hardness, friability, drug content, and in-vitro drug release using USP dissolution apparatus type-2 (paddle) by using HPLC method. Drug release from the matrix was found to decrease with increase in polymer concentration in intra and extra granulation, where the polymer concentration was employed from 20-50%w/w of the average tablet weight.

Tanmoy ghosh et. al.

Studied on “Formulation and evaluation of sustained release Omeprazole succinate matrix tablets by direct compression process using kollidon SR”. Sustained release matrix tablets were prepared by different concentrations of directly compressible grade and controlled release polymer of kollidon SR. Finally concluded that kollidon SR can be utilized for effective production of controlled release Omeprazole Succinate matrix tablets by direct compression process using an optimum concentration for desired release profile.

LITERATURE REVIEW

Ozturk AG et. al 51: studied on “Fabrication and in vitro evaluation of porous osmotic pump based controlled drug

delivery of Omeprazole succinate”. The purpose of investigation was that an osmotically controlled oral drug delivery system utilizes osmotic pressure for controlled delivery of active agents. The osmotic control release of tablet was prepared by two different approaches; one using an osmotic agent and another using a swelling agent. The effect of concentration of osmotic agent and swelling agent on in vitro release was studied and was found that drug release depend on both these factors.

Narisawa S et. al 52: studied on “Formulation and evaluation of Omeprazole succinate controlled release tablets

using natural and synthetic polymer”. The objective of the present study is to develop controlled release tablets of Omeprazole succinate using natural polymer-guar gum and synthetic polymer-carbopol as a rate controlling polymers for treatment of hypertension, angina pectoris, cardiac arrthymias. It was also desired to study the effect of polymer concentration. The formulations are made by employing the conventional wet granulation method, to achieve prolonged release of medicaments. The formulation containing 5% carbopol-934 released 89% of the drug in 12hours.

DRUG PROFILE Name: Omeprazole  Brand Names Prilosec and Losec Molecular Weight: 345.42 g/mol Chemical Formula: C17H19N3O3S Structure:

IUPAC Name: 6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1H- benzimidazole

Description: This is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL cholesterol.

Drug category:  gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome

Omeprazole (Prilosec, Zegerid) belongs to group of drugs called proton pump inhibitors. It decreases the amount of acid produced in the stomach.

Omeprazole is used to treat symptoms of Gastro Esophageal Reflux Disease (GERD) and other conditions caused by excess stomach acid. It is also used to promote healing of erosive esophagitis (damage to your esophagus caused by stomach acid).

Omeprazole may also be given together with antibiotics to treat gastric ulcer caused by infection with helicobacter pylori (H. pylori).

Omeprazole is not for immediate relief of heartburn symptoms.

AIM AND OBJECTIVESo The present project is proposed to formulation and evaluation of omeprazole floating tablets.

o Omeprazole used in combination with antacids promotes local delivery of these drugs to the receptor of the parietal cell wall. Local delivery also increases the stomach wall receptor site bioavailability and increases the drugs’ ability to reduce acid secretion.

  The objectives of the present investigations are:

To carry out an extensive literature review on omeprazole formulations. To perform pre-formulation studies and to check whether the drug is suitable for direct compression

technique. To characterization of developed tablets for hardness, thickness, weight variation, dimensions, etc., To optimize the best formulation based on the statistical optimization.  To optimize a safe, effective and stable dosage form of omeprazole floating tablets. The stability data of the optimized formulation indicated that the formulation showed sufficient

stability upon storage.

PLAN OF WORK It was planned to carryout study in the sequences below: Extensive literature review Formulation and evaluation of omeprazole floating tablets. Formulation and evaluation of omeprazole floating tablets.

-Angle of repose

-Bulk density

-Tapped density Evaluation of Post compression characteristics of omeprazole of floating tablets.

-Hardness -

-Friability

Weight variation  Selection of best formulation on the basis of evaluation of omeprazole floating tablets.

MATERIALS AND METHODS

List of Equipments

Equipment Company

Electronic Balance MettlerToledo, USA

B.D. Apparatus Cambell electronics’, Mumbai

UV-Vis Spectrophotometer LabIndia

Tablet Compression Machine Jaguarl Machinery Company, Mumbai

Friability Test Apparatus USP23 Roche Friabilator LabIndia, Mumbai

Tablet Hardness Tester Stokes Monsanto Hardness Tester,

Composition of different floating tablet formulations of Omeprozole:

Formulation code F1 F2 F3 F4 F5 F6

Ingredients(mg)

Omeprazole 40 40 40 40 40 40HPMC K 4 M

80 80 - - 40 40HPMC K 15 M - - 80 80 40 40

Sodium

bicarbonate

20 10 20 10 20 10

Mg. Stearate2

2 2 2 2 2

Lactose20

20 20 20 20 20

Talc2

2 2 2 2 2

PVK-30 30 30 30 30 30 30

Citric acid 10 20 10 20 10 20

Preparation of Floating Tablets :  Effervescent Floating tablets containing Omeprazole were prepared by

direct compression technique using varying concentrations of different grades of polymers (HPMC K4

M and HPMC K15 M) with sodium bicarbonate and citric acid. All the ingredients were accurately weighed as show in Table and passed

through different mesh sieves accordingly. Then, except Magnesium stearate and talc all other ingredients were

blended uniformly in glass mortar After sufficient mixing of drug as well as other components, Magnesium stearate and talc was added, as post lubricant, and further mixed for additional 2-3 minutes.

The blend was characterized for the different physical parameters such as bulk density, Tapped density. The tablets were compressed using rotary tablet machine.

The weights of the tablets were kept constant for all formulation. Tablets were compressed at 200 mg weight.

PRECOMPRESSIONAL PARAMETERS

Bulk density Tapped density Carr’s index Hausner’s ratio  Angle of repose ()

POST COMPRESSIONAL PARAMETERS

1 Weight variation 2 Hardness 3 Friability 4 Content uniformity 5 In-Vitro Dissolution.

RESULTS AND DISCUSSION Precompressional parameters

Formulation

code/Parameter

Bulk

density

Tapped

density

Angle of

repose

Compressib

ility index

Hausners

ratio

F1 0.55 0.65 28.5 15.5 1.02

F2 0.45 0.67 26.5 17.5 1.05

F3 0.51 0.71 29.5 19.8 1.10

F4 0.52 0.65 28.9 16.4 1.03

F5 0.49 0.70 26.6 15.6 1.15

F6 0.52 0.66 30.5 16.9 1.23

Post compressional parameters

Formulation

code/Parameter

Hardness Weight

variation

Friability Drug

content (%)

F1 3.8 Pass 0.54 91.3

F2 3.74 Pass 0.75 90.6

F3 3.95 Pass 0.64 96.0

F4 3.7 Pass 0.44 96.6

F5 3.9 Pass 0.77 91.33

F6 3.6 Pass 0.65 95.3

Batch 1hr 2hr 3hr 4hr 5hr 6hr 7hr

F1 17.95 23.30 38.90 48.81 61.70 86.88 91.79

F2 23.92 28.90 35.88 48.85 65.78 83.72 90.69

F3 15.94 25.91 43.85 55.81 61.69 72.75 88.70

F4 21.92 37.87 43.80 62.69 68.77 76.74 83.72

F5 23.82 30.89 41.86 58.80 63.78 80.73 85.71

F6 19.93 31.89 53.82 58.80 62.79 73.75 94.68

Cumulative % drug released of F1 to F7 (0.1N HCl) Formulation

InVitro drug Release

1hr 2hr 3hr 4hr 5hr 6hr 7hr 0

10

20

30

40

50

60

70

80

90

100

F1 F2 F3 F4 F5 F6

Time(Hrs)

%D

rug

Rel

ease

Cumulative drug release F1-F6

DRUG RELEASE KINETICS   Zero order Frist order Highuchi peppas

F.CODE R2 R2 R2 R2

F1 0.9839 0.9337 0.9766 0.9775

F2 0.9896 0.8732 0.9086 0.982

F3 0.8047 0.9683 0.9335 0.969

F4 0.885 0.9656 0.9807 0.9828

F5 0.9105 0.982 0.9807 0.9854

F6 0.8583 0.9931 0.9539 0.9618

Conclusion

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